Genetic Variant NM_014584.3:c.1008G>T (chr14-52653116-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014584.3(ERO1A):c.1008G>T(p.Gln336His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,446,850 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 1 hom. )

Consequence

ERO1A
NM_014584.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.137

Publications

0 publications found

Variant links:

Genes affected

ERO1A (HGNC:13280): (endoplasmic reticulum oxidoreductase 1 alpha) Enables oxidoreductase activity. Involved in chaperone cofactor-dependent protein refolding. Located in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

ERO1A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10520318).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014584.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERO1A	NM_014584.3	MANE Select	c.1008G>T	p.Gln336His	missense	Exon 12 of 16	NP_055399.1	Q96HE7
ERO1A	NM_001382464.1		c.1047G>T	p.Gln349His	missense	Exon 13 of 17	NP_001369393.1
ERO1A	NM_001382465.1		c.996G>T	p.Gln332His	missense	Exon 11 of 15	NP_001369394.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ERO1A	ENST00000395686.8	TSL:1 MANE Select	c.1008G>T	p.Gln336His	missense	Exon 12 of 16	ENSP00000379042.3	Q96HE7
ERO1A	ENST00000556358.5	TSL:2	c.-16G>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 6	ENSP00000450655.1	G3V2H0
ERO1A	ENST00000964628.1		c.1047G>T	p.Gln349His	missense	Exon 13 of 17	ENSP00000634687.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000798

AC:

AN:

250606

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1446850

Hom.:

Cov.:

AF XY:

0.00000971

AC XY:

AN XY:

720738

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33174

American (AMR)

AF:

0.00

AC:

AN:

44660

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26008

East Asian (EAS)

AF:

0.000152

AC:

AN:

39522

South Asian (SAS)

AF:

0.0000116

AC:

AN:

85886

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5710

European-Non Finnish (NFE)

AF:

9.10e-7

AC:

AN:

1098650

Other (OTH)

AF:

0.000134

AC:

AN:

59872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.38

Eigen

Benign

-0.77

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.76

M_CAP

Benign

0.0080

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

-0.14

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.0

REVEL

Benign

0.047

Sift

Benign

0.066

Sift4G

Uncertain

0.022

Polyphen

0.012

Vest4

0.094

MutPred

0.51

Loss of methylation at K334 (P = 0.1065)

MVP

0.10

MPC

0.29

ClinPred

0.063

GERP RS

-0.65

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.10

gMVP

0.49

Mutation Taster

=56/44

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over